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HEXACHLOROPHENE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Hexachlorophene has bacteriostatic agent against staphylococci and other gram positive bacteria. It is approved as a surgical scrub and bacteriostatic skin cleanser. Because of its potential toxicity, its use is generally restricted.

Specific Substances

    1) Hexachlorophene
    2) Hexachlorophane
    3) G-11
    4) HCP
    5) 2,2'Methylene bis (3,4,6-trichlorophenol)
    6) Molecular Formula: C13-H6-Cl6-O2
    7) CAS 70-30-4
    8) HCP (HEXACHLOROPHENE)
    9) HILO FLEA POWDER WITH ROTENONE AND DICHLOROPHRENE
    1.2.1) MOLECULAR FORMULA
    1) C13-H6-Cl6-O2

Available Forms Sources

    A) FORMS
    1) Hexachlorophene is a tasteless and generally odorless crystalline solid (from benzene) or a white crystalline or powder (Budavari, 1996; Lewis, 2000).
    2) Hexachlorophene is available in the United States as a 3% topical liquid (Prod Info pHisoHex(R) topical detergent cleanser, 2011).
    3) Since 1974, US FDA regulations limit hexachlorophene in cosmetics to less than 0.1%. Trade names include pHisoHex (Winthrop-Breon), Bilevon, Dermadex, Exofene, Gamophen, Surgi-Cen, and Surofene (among many others) (RTECS , 2002).
    B) USES
    1) Hexachlorophene is approved as a surgical scrub and bacteriostatic skin cleanser. It is indicated to control an outbreak of gram-positive infection where other infection control measures have failed (Prod Info pHisoHex(R) topical detergent cleanser, 2011).
    2) It has also been used as an additive in the feed and drinking water of animals and/or for the treatment of food-producing animals (Lewis, 2000).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Hexachlorophene is approved as a surgical scrub and bacteriostatic skin cleanser. It is indicated to control an outbreak of gram-positive infection where other infection control measures have failed.
    B) PHARMACOLOGY: Hexachlorophene is a bacteriostatic agent against staphylococci and other gram positive bacteria.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) Dermatitis and photosensitivity may occur following topical use of hexachlorophene.
    E) WITH POISONING/EXPOSURE
    1) DERMAL: Dermal application of highly concentrated (greater than 3%) preparations on several occasions or repeated applications of less concentrated preparations, especially in neonates or to damaged skin, may result in significant toxicity. Nausea, vomiting, anorexia, diarrhea, and lethargy frequently occur as early signs of toxicity. In one study, an erythematous desquamative rash was the most common sign of topical hexachlorophene toxicity (reported in 93% of 204 children dermally exposed to 6.3% hexachlorophene powder). The rash may precede or follow the onset of neurologic abnormalities. In patients with significant CNS toxicity (eg, coma, seizures), cerebral edema is almost always present, sometimes sufficient to cause herniation and death.
    2) INGESTION: Acute ingestion of large amounts (greater than 30 mL by adults) or repeated ingestion of small amounts may cause significant toxicity or death. Anorexia, vomiting, abdominal pain, diarrhea, dehydration, seizures, hypotension, shock, and death have been reported following accidental ingestion of 1 to 4 oz (30 to 120 mL) of 3% hexachlorophene. Other reported effects include bradycardia, blindness, muscular fasciculations, irritability, weakness, hypertonicity, transverse myelopathy of the spinal cord, cranial nerve palsies, choreoathetosis, and cardiorespiratory arrest.
    0.2.3) VITAL SIGNS
    A) Low grade fever is common.
    0.2.20) REPRODUCTIVE
    A) Hexachlorophene is classified as FDA Pregnancy Category C. It has been suspected of being teratogenic, based on experimental animal data with developmental abnormalities of the craniofacial area and CNS, as well as a variety of other adverse reproductive effects.
    B) The AMA Council on Scientific Affairs concluded that pregnant women should not use hexachlorophene-containing products.

Laboratory Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs and mental status.
    C) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with severe diarrhea and/or vomiting. Manage mild hypotension with IV fluids.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Treat seizures with IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur. Treat severe hypotension with IV fluids, dopamine, or norepinephrine. Where elevated intracranial pressure or cerebral edema are present, treatment should be initiated. Controlled hyperventilation, osmotic diuretics and/or dexamethasone may prove to be useful. Based on hexachlorophene's lipid solubility, intravenous lipid infusion might be useful in the treatment of patients with severe toxicity, but there are no published reports of its use.
    C) DECONTAMINATION
    1) PREHOSPITAL: Prehospital gastrointestinal decontamination is not recommended because of the potential for CNS depression or seizures and subsequent aspiration. DERMAL: Vigorous washing with soap and water is necessary. Hexachlorophene is well absorbed dermally and may remain on the skin following simple rinsing due to poor solubility in water.
    2) HOSPITAL: Administer activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
    D) AIRWAY MANAGEMENT
    1) Ensure adequate ventilation and perform endotracheal intubation early in patients with significant CNS depression or persistent seizures.
    E) ANTIDOTE
    1) None
    F) LIPID EMULSION
    1) Based on hexachlorophene's lipid solubility, intravenous lipid infusion might be useful in the treatment of patients with severe toxicity, but there are no published reports of its use. Patients who develop significant cardiovascular toxicity may be treated with intravenous lipids. Administer 1.5 mL/kg of 20% lipid emulsion over 2 to 3 minutes as an IV bolus, followed by an infusion of 0.25 mL/kg/min. Evaluate the patient's response after 3 minutes at this infusion rate. The infusion rate may be decreased to 0.025 mL/kg/min (ie, 1/10 the initial rate) in patients with a significant response. This recommendation has been proposed because of possible adverse effects from very high cumulative rates of lipid infusion. Monitor blood pressure, heart rate, and other hemodynamic parameters every 15 minutes during the infusion. If there is an initial response to the bolus followed by the re-emergence of hemodynamic instability during the lowest-dose infusion, the infusion rate may be increased back to 0.25 mL/kg/min or, in severe cases, the bolus could be repeated. A maximum dose of 10 mL/kg has been recommended by some sources. Where possible, lipid resuscitation therapy should be terminated after 1 hour or less, if the patient's clinical status permits. In cases where the patient's stability is dependent on continued lipid infusion, longer treatment may be appropriate.
    G) ENHANCED ELIMINATION
    1) Hemodialysis is probably not effective due to rapid redistribution of hexachlorophene into body lipid stores.
    H) PATIENT DISPOSITION
    1) HOME CRITERIA: Asymptomatic patients with limited dermal exposure can probably be managed at home. Asymptomatic patients with inadvertent ingestion of a lick or taste can also be managed at home. Acute ingestion of large amounts (greater than 30 mL by adults, more than a lick or taste by chldren) or repeated ingestion of small amounts may cause significant toxicity or death. These patients should be referred to a healthcare facility.
    2) OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, should be evaluated in a health care facility. Patients that remain asymptomatic can be discharged.
    3) ADMISSION CRITERIA: Patients should be admitted for severe vomiting, profuse diarrhea, severe abdominal pain, dehydration, electrolyte abnormalities, significant CNS depression, or persistent seizures.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    I) PITFALLS
    1) When managing a suspected overdose, the possibility of multidrug involvement should be considered.
    J) PHARMACOKINETICS
    1) Absorption: rapidly and effectively absorbed following ingestion. Skin absorption is also effective. Hexachlorophene has a high lipid/water partition coefficient and rapidly redistributes into lipoid tissues, including the CNS. Metabolism: liver. Elimination half-life: about 24 hours, with a range of 6 to 44 hours.
    K) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that cause CNS depression, hypotension, or seizures.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
    0.4.4) EYE EXPOSURE
    A) Irrigate the eyes for at least 15 minutes using only low pressure normal saline, with at least 1 liter per exposed eye. If normal saline is not available, immediately irrigate with similar quantities of tepid tap water.
    B) If symptoms persist, the patient should be referred to a health care facility for ophthalmological evaluation and management.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Vigorous washing with soap and water is necessary, because hexachlorophene is well absorbed through intact skin and may remain on the skin following simple rinsing due to its poor water solubility.

Range Of Toxicity

    A) TOXICITY: The minimal toxic or lethal dose following acute ingestion or repeated skin application is not well defined. Acute ingestion of large amounts (greater than 30 mL by adults) or repeated ingestion of small amounts may cause significant toxicity or death. Anorexia, vomiting, abdominal pain, diarrhea, dehydration, seizures, hypotension, shock, and death have been reported following inadvertent ingestion of 1 to 4 oz (30 to 120 mL) of 3% hexachlorophene. Following ingestion of 4 to 5 oz (120 to 150 mL) of a 3% hexachlorophene solution, a 6-year-old child became obtunded. Hypotension and seizures ensued, and death occurred within an hour of ingestion.
    B) THERAPEUTIC DOSES: 5 mL emulsion used topically for 3 minutes.

Clinical Effects

Summary Of Exposure

    A) USES: Hexachlorophene is approved as a surgical scrub and bacteriostatic skin cleanser. It is indicated to control an outbreak of gram-positive infection where other infection control measures have failed.
    B) PHARMACOLOGY: Hexachlorophene is a bacteriostatic agent against staphylococci and other gram positive bacteria.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) Dermatitis and photosensitivity may occur following topical use of hexachlorophene.
    E) WITH POISONING/EXPOSURE
    1) DERMAL: Dermal application of highly concentrated (greater than 3%) preparations on several occasions or repeated applications of less concentrated preparations, especially in neonates or to damaged skin, may result in significant toxicity. Nausea, vomiting, anorexia, diarrhea, and lethargy frequently occur as early signs of toxicity. In one study, an erythematous desquamative rash was the most common sign of topical hexachlorophene toxicity (reported in 93% of 204 children dermally exposed to 6.3% hexachlorophene powder). The rash may precede or follow the onset of neurologic abnormalities. In patients with significant CNS toxicity (eg, coma, seizures), cerebral edema is almost always present, sometimes sufficient to cause herniation and death.
    2) INGESTION: Acute ingestion of large amounts (greater than 30 mL by adults) or repeated ingestion of small amounts may cause significant toxicity or death. Anorexia, vomiting, abdominal pain, diarrhea, dehydration, seizures, hypotension, shock, and death have been reported following accidental ingestion of 1 to 4 oz (30 to 120 mL) of 3% hexachlorophene. Other reported effects include bradycardia, blindness, muscular fasciculations, irritability, weakness, hypertonicity, transverse myelopathy of the spinal cord, cranial nerve palsies, choreoathetosis, and cardiorespiratory arrest.

Vital Signs

    3.3.1) SUMMARY
    A) Low grade fever is common.
    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) FEVER: Low grade fever is common.
    2) With highly concentrated 6.3% hexachlorophene-containing baby powder exposure, 44% (99/204) of patients had a low-grade to moderate fever, although at times the temperature exceeded 39 degrees C (Martin-Bouyer, 1982).

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) BLINDNESS: A 7-year-old, 23 kg boy who received 43 mg/kg of hexachlorophene over 52 hours developed blindness (Boehm & Czajka, 1979; Slamovits, 1980).
    2) OPTIC ATROPHY: A 31-year-old who ingested 10 to 15 mg of 3% hexachlorophene emulsion daily for 10 months gradually developed optic atrophy (Boehm & Czajka, 1979; Slamovits, 1980).
    3) IRRITATION: Eye irritation may occur following ocular exposure.

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypotension has been reported following ingestion of 4 to 5 oz of 3% hexachlorophene over 52 hours by a 6-year-old child (Lustig, 1963).
    b) INGESTION: Hypotension, shock, and death have been reported following the inadvertent ingestion of 1 to 4 oz of 3% hexachlorophene (Prod Info pHisoHex(R) topical detergent cleanser, 2011).
    B) BRADYCARDIA
    1) WITH POISONING/EXPOSURE
    a) Bradycardia has been reported following ingestion (Boehm & Czajka, 1979).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) RESPIRATORY FAILURE
    1) WITH POISONING/EXPOSURE
    a) Respiratory failure has been reported following ingestion of 43 mg/kg over 52 hours (Boehm & Czajka, 1979).
    B) BRONCHOSPASM
    1) WITH POISONING/EXPOSURE
    a) OCCUPATIONAL ASTHMA: Hexachlorophene inhalation exposure has resulted in rare cases of occupational asthma (Malo & Bernstein, 1993).
    1) A 43-year-old pediatric nurse with 15 years of exposure to hexachlorophene powder developed occupational asthma (Nagy & Orosz, 1984).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) NEUROTOXICITY
    1) WITH POISONING/EXPOSURE
    a) Onset of neurologic abnormalities frequently begins within hours of a large oral dose, but may be delayed for days, especially following smaller repeated dermal exposures.
    B) DROWSY
    1) WITH POISONING/EXPOSURE
    a) Lethargy is one of the most common manifestations of hexachlorophene poisoning. Lethargy occurred in 37% (83/204) of children with toxicity from highly concentrated (6.3%) hexachlorophene-containing baby powder (Martin-Bouyer, 1982).
    C) FEELING NERVOUS
    1) WITH POISONING/EXPOSURE
    a) Irritability is one of the most common toxic manifestations of hexachlorophene poisoning. Irritability occurred in 33% (75/204) of children with toxicity from highly concentrated (6.3%) hexachlorophene containing baby powder (Martin-Bouyer, 1982).
    D) COMA
    1) WITH POISONING/EXPOSURE
    a) Coma is a common toxic manifestation of hexachlorophene poisoning. Coma occurred in 25% (55/204) of children with toxicity from highly concentrated (6.3%) hexachlorophene containing baby powder (Martin-Bouyer, 1982).
    E) SPASMODIC MOVEMENT
    1) WITH POISONING/EXPOSURE
    a) Muscular fasciculations are a common toxic manifestation of hexachlorophene poisoning. These may progress to weakness, hypertonicity, transverse myelopathy of the spinal cord, cranial nerve palsies, and choreoathetosis (Goutieres & Aicardi, 1977).
    F) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Seizures are common toxic manifestations of hexachlorophene poisoning (HSDB , 2002).
    b) INGESTION: Seizure has been reported following the inadvertent ingestion of 1 to 4 oz of 3% hexachlorophene (Prod Info pHisoHex(R) topical detergent cleanser, 2011).
    G) CEREBRAL EDEMA
    1) WITH POISONING/EXPOSURE
    a) In patients with significant CNS neurologic toxicity, cerebral edema is almost always present, sometimes sufficient to cause herniation and death (Goutieres & Aicardi, 1977; HSDB , 2002).
    b) NEONATES: Postmortem pathologic examination of neonates repeatedly exposed to hexachlorophene has revealed vacuolization of the CNS white matter, corresponding to intramyelinic edema without actual demyelination (spongiform encephalomalacia). The correlation between these findings and clinical status remains controversial. Most patients who did not succumb from acute toxicity had clinically complete reversal of the acute neurologic abnormalities. The potential for late-onset learning disability or reproductive abnormalities remains unresolved (Powell et al, 1973; Anderson et al, 1981) Anderson et al, 1981; (Plueckhahn & Collins, 1976; Martin-Bouyer et al, 1982; Goutieres & Aicardi, 1977; Weiss, 1978; Garcia-Bunuel, 1982a; Garcia-Bunuel, 1982b; Goldstein, 1982).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) NEUROPATHY
    a) In experimental animals, excessive doses of hexachlorophene result in neurotoxicity (HSDB , 2002).
    b) Reversible vacuolar changes mainly affecting the myelin of the brain and spinal cord have been reported (RTECS , 2002; HSDB , 2002).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) VOMITING
    1) WITH POISONING/EXPOSURE
    a) Vomiting was reported in 34% (77/204) of children exposed to highly concentrated (6.3%) hexachlorophene containing baby powder (Martin-Bouyer, 1982). Vomiting and diarrhea usually are among the first manifestations of hexachlorophene poisoning.
    b) INGESTION: Vomiting has been reported following the inadvertent ingestion of 1 to 4 oz of 3% hexachlorophene (Prod Info pHisoHex(R) topical detergent cleanser, 2011).
    B) DIARRHEA
    1) WITH POISONING/EXPOSURE
    a) Diarrhea developed in 29% (65/204) of children exposed to highly concentrated (6.3%) hexachlorophene containing baby powder (Martin-Bouyer, 1982).
    b) INGESTION: Diarrhea and dehydration have been reported following the inadvertent ingestion of 1 to 4 oz of 3% hexachlorophene (Prod Info pHisoHex(R) topical detergent cleanser, 2011).
    C) LOSS OF APPETITE
    1) WITH POISONING/EXPOSURE
    a) Anorexia was reported in 33% of the hexachlorophene-exposed children exposed to highly concentrated (6.3%) hexachlorophene containing baby powder (Martin-Bouyer, 1982).
    b) INGESTION: Anorexia has been reported following the inadvertent ingestion of 1 to 4 oz of 3% hexachlorophene (Prod Info pHisoHex(R) topical detergent cleanser, 2011).
    D) ABDOMINAL PAIN
    1) WITH POISONING/EXPOSURE
    a) INGESTION: Abdominal pain has been reported following the inadvertent ingestion of 1 to 4 oz of 3% hexachlorophene (Prod Info pHisoHex(R) topical detergent cleanser, 2011).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) LIVER DAMAGE
    1) ANIMAL STUDIES: Mice given 60 mg/kg/day (intragastrically) developed degenerative liver changes (Prasad et al, 1987c). There was a steep rise in blood and brain ammonia levels at this dose (Prasad et al, 1987c).

Reproductive

    3.20.1) SUMMARY
    A) Hexachlorophene is classified as FDA Pregnancy Category C. It has been suspected of being teratogenic, based on experimental animal data with developmental abnormalities of the craniofacial area and CNS, as well as a variety of other adverse reproductive effects.
    B) The AMA Council on Scientific Affairs concluded that pregnant women should not use hexachlorophene-containing products.
    3.20.2) TERATOGENICITY
    A) CONGENITAL ANOMALY
    1) Hexachlorophene has been suspected of being teratogenic, based on experimental animal data with developmental abnormalities of the craniofacial area and CNS, as well as a variety of other adverse reproductive effects (RTECS , 2002). There was also an unexpectedly high incidence of malformations in a Swedish chronic disease hospital where hexachlorophene was extensively used (HSDB , 2002).
    a) However, a more comprehensive, better controlled study failed to confirm the initial observation in humans (Baltzar, 1979).
    b) The AMA Council on Scientific Affairs concluded that pregnant women should not use hexachlorophene-containing products (AMA, 1985).
    B) ANIMAL STUDIES
    1) RATS: Teratogenic and embryotoxic effects have been reported with oral or vaginally instilled doses. Malformations (angulated ribs, cleft palate, and micro- and anophthalmia) were also observed in rats administered doses 500 mg/kg or 20 to 30 mg/kg body weight/day by gavage. No effects were observed in 3 generations of rats administered doses up to 50 mg/kg (Prod Info pHisoHex(R) topical detergent cleanser, 2012).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Hexachlorophene is classified as FDA Pregnancy Category C (Prod Info pHisoHex(R) topical detergent cleanser, 2012).
    B) ANIMAL STUDIES
    1) RATS: A reduction in litter size was also observed in rats administered doses 500 mg/kg or 20 to 30 mg/kg body weight/day by gavage. No effects were observed in 3 generations of rats administered doses up to 50 mg/kg. Placental transfer of hexachlorophene has also been observed in rats (Prod Info pHisoHex(R) topical detergent cleanser, 2012).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Hexachlorophene appears in the breast milk of rats (Kennedy, 1977) and in human breast milk (West, 1975; HSDB , 2002).
    2) Because many drugs are excreted into human milk, either breastfeeding or the drug should be discontinued, taking into account the importance of the drug to the mother (Prod Info pHisoHex(R) topical detergent cleanser, 2012).
    B) ANIMAL STUDIES
    1) RATS: Excretion of hexachlorophene in milk has been observed in rats (Prod Info pHisoHex(R) topical detergent cleanser, 2012).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) HAMSTERS: No reproductive effects were observed in hamsters (Prod Info pHisoHex(R) topical detergent cleanser, 2012).
    2) RATS: Reduced fertility due to the inability to ejaculate was observed in neonatal rats administered a 3% topical solution (Prod Info pHisoHex(R) topical detergent cleanser, 2012).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS70-30-4 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) IARC Classification
    a) Listed as: Hexachlorophene
    b) Carcinogen Rating: 3
    1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    3.21.3) HUMAN STUDIES
    A) SOFT TISSUE SARCOMA
    1) A malignant fibrous histiocytoma was described in a 34-year-old woman who worked with hexachlorophene for 6 years as a cleaner and hospital nursing assistant (Hardell, 1992). The dioxin contaminant was postulated as being responsible.
    B) NON-HODGKIN'S LYMPHOMA
    1) Eight cases of non-Hodgkin's lymphoma were reported in Swedish hospital workers exposed to hexachlorophene. Latent periods were from 14 to 38 years (Hardell & Erickson, 1992).
    3.21.4) ANIMAL STUDIES
    A) NEOPLASM
    1) Hexachlorophene was neoplastic by RTECS criteria in rats (respiratory tract tumors) and an equivocal tumorigenic agent by RTECS criteria in mice (skin and appendages tumors) (RTECS , 2002).
    B) LACK OF EFFECT
    1) In a bioassay of Fischer 344 rats, hexachlorphene did not induce malignant or benign tumors during a chronic feeding study (NCI, 1978).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) GENERALIZED EXFOLIATIVE DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) An erythematous desquamative rash was the most common sign of topical hexachlorophene toxicity (reported in 93% of 204 children dermally exposed to 6.3% hexachlorophene powder). The rash may precede or follow the onset of neurologic abnormalities (Martin-Bouyer, 1982; Goutieres & Aicardi, 1977).
    B) DERMATITIS
    1) WITH THERAPEUTIC USE
    a) Dermatitis may occur following topical use (Prod Info pHisoHex(R) topical detergent cleanser, 2011).
    C) PHOTOSENSITIVITY
    1) WITH THERAPEUTIC USE
    a) Photosensitivity may occur following topical use (Prod Info pHisoHex(R) topical detergent cleanser, 2011).
    D) ERUPTION
    1) WITH POISONING/EXPOSURE
    a) Strong concentrations may be irritating, but ordinary use of 1% to 2% solutions is generally not (Lewis, 2000).
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) In guinea pigs treated dermally with 50 mg/kg of hexachlorophene for 7 to 30 days, sloughing, inflammatory and epidermal regenerative changes, petechial hemorrhages, and extensive destruction of the dermis, hair follicles, and sebaceous glands were noted (Mathur et al, 1992).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs and mental status.
    C) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    4.1.2) SERUM/BLOOD
    A) TOXICITY
    1) Death has been reported following levels as low as 0.78 mcg/mL in a child, but adults have remained asymptomatic with levels of 2.16 mcg/mL (Lockhart, 1972).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients should be admitted for severe vomiting, profuse diarrhea, severe abdominal pain, dehydration, electrolyte abnormalities, significant CNS depression, or persistent seizures.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Asymptomatic patients with limited dermal exposure can probably be managed at home. Asymptomatic patients with inadvertent ingestion of a lick or taste can also be managed at home. Acute ingestion of large amounts (greater than 30 mL by adults, more than a lick or taste) or repeated ingestion of small amounts may cause significant toxicity or death. These patients should be referred to a healthcare facility.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate overdose, and those who are symptomatic, should be evaluated in a health care facility. Patients that remain asymptomatic can be discharged.

Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs and mental status.
    C) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Prehospital gastrointestinal decontamination is not recommended because of the potential for CNS depression or seizures and subsequent aspiration.
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) Activated charcoal has been reported to bind hexachlorophene (Picchioni et al, 1972).
    2) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    2) Monitor vital signs and mental status.
    3) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    B) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    C) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    D) FAT EMULSION
    1) SUMMARY
    a) Based on hexachlorophene's lipid solubility, intravenous lipid infusion might be useful in the treatment of patients with severe toxicity, but there are no published reports of its use.
    2) Intravenous lipid emulsion (ILE) has been effective in reversing severe cardiovascular toxicity from local anesthetic overdose in animal studies and human case reports. Several animal studies and human case reports have also evaluated the use of ILE for patients following exposure to other drugs. Although the results of these studies are mixed, there is increasing evidence that it can rapidly reverse cardiovascular toxicity and improve mental function for a wide variety of lipid soluble drugs. It may be reasonable to consider ILE in patients with severe symptoms who are failing standard resuscitative measures (Lavonas et al, 2015).
    3) The American College of Medical Toxicology has issued the following guidelines for lipid resuscitation therapy (LRT) in the management of overdose in cases involving a highly lipid soluble xenobiotic where the patient is hemodynamically unstable, unresponsive to standard resuscitation measures (ie, fluid replacement, inotropes and pressors). The decision to use LRT is based on the judgement of the treating physician. When possible, it is recommended these therapies be administered with the consultation of a medical toxicologist (American College of Medical Toxicology, 2016; American College of Medical Toxicology, 2011):
    a) Initial intravenous bolus of 1.5 mL/kg 20% lipid emulsion (eg, Intralipid) over 2 to 3 minutes. Asystolic patients or patients with pulseless electrical activity may have a repeat dose, if there is no response to the initial bolus.
    b) Follow with an intravenous infusion of 0.25 mL/kg/min of 20% lipid emulsion (eg, Intralipid). Evaluate the patient's response after 3 minutes at this infusion rate. The infusion rate may be decreased to 0.025 mL/kg/min (ie, 1/10 the initial rate) in patients with a significant response. This recommendation has been proposed because of possible adverse effects from very high cumulative rates of lipid infusion. Monitor blood pressure, heart rate, and other hemodynamic parameters every 15 minutes during the infusion.
    c) If there is an initial response to the bolus followed by the re-emergence of hemodynamic instability during the lowest-dose infusion, the infusion rate may be increased back to 0.25 mL/kg/min or, in severe cases, the bolus could be repeated. A maximum dose of 10 mL/kg has been recommended by some sources.
    d) Where possible, LRT should be terminated after 1 hour or less, if the patient's clinical status permits. In cases where the patient's stability is dependent on continued lipid infusion, longer treatment may be appropriate.
    E) CEREBRAL EDEMA
    1) In patients with CNS neurologic abnormalities, the possibility of elevated intracranial pressure or cerebral edema should be considered and treatment initiated to reduce intracranial pressure.
    2) CLINICAL IMPLICATIONS
    a) Cerebral edema and elevated intracranial pressure (ICP) may occur. Emergent management includes head elevation and administration of mannitol; hyperventilation should be performed if there is evidence of impending herniation.
    3) MONITORING
    a) Patients will usually require endotracheal intubation and mechanical ventilation. Monitor intracranial pressure, cerebral perfusion pressure and cerebral blood flow.
    4) TREATMENT
    a) Most information on the treatment of cerebral edema is derived from studies of traumatic brain injury.
    5) MANNITOL
    a) ADULT/PEDIATRIC DOSE: 0.25 to 1 gram/kilogram intravenously over 10 to 15 minutes (None Listed, 2000).
    b) AVAILABLE FORMS: Mannitol injection (5%, 10%, 15%, 20%, 25%).
    c) MAJOR ADVERSE REACTIONS: Congestive heart failure, hypernatremia, hyponatremia, hyperkalemia, renal failure, pulmonary edema, and allergic reactions.
    d) PRECAUTIONS: Contraindicated in well-established anuria or impaired renal function not responding to a test dose, pulmonary edema, CHF, severe dehydration; caution in progressive oliguria and azotemia. Do not add to whole blood for transfusions; enhanced neuromuscular blockade has occurred with tubocurarine. Keep serum osmolarity below 320 mOsm.
    e) MONITORING PARAMETERS: Renal function, urine output, fluid balance, serum potassium levels, serum osmolarity, and CVP.
    6) HYPERTONIC SALINE
    a) Preliminary studies suggest that hypertonic saline (7.5% saline/6% dextran) 100 ml reduced ICP more effectively than 200 mL of 20% mannitol in adults with elevated ICP after traumatic brain injury(Battison et al, 2005).
    7) ELEVATION
    a) Elevation of the head of the bed to approximately 30 degrees decreases ICP and improves cerebral perfusion pressure (Meixensberger et al, 1997; Schneider et al, 1993; Feldman et al, 1992).
    8) MECHANICAL DECOMPRESSION
    a) Early surgical decompression, ventriculostomy with CSF drainage, or craniectomy may be useful in patients with persistent elevation of ICP (Sahuquillo & Arikan, 2006; Sakai et al, 1998; Polin et al, 1997; Taylor et al, 2001). Most experience with these modalities has been in patients with traumatic brain injury.
    9) HYPERVENTILATION
    a) SUMMARY: Hyperventilation has been associated with adverse outcomes and should not be performed routinely (Muizelaar et al, 1991). It is indicated in patients who have clinical evidence of herniation or if there is intracranial hypertension refractory to sedation, paralysis, CSF drainage and osmotic diuretics (None Listed, 2000a).
    b) RECOMMENDATION:
    1) The PCO2 must be controlled in the range of 25 torr; further lowering of PCO2 may create undesirable effects secondary to local tissue hypoxia.
    2) End-tidal CO2 tension, correlated with an initial ABG measurement, provides a noninvasive means of monitoring PCO2 (Mackersie & Karagianes, 1990).
    3) Most authorities advise that hyperventilation should be considered a temporizing measure only; SUSTAINED hyperventilation should be avoided (Am Acad Neurol, 1997; Bullock et al, 1996; Kirkpatrick, 1997).

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) The patient should be removed from further exposure to the source of inhaled hexachlorophene, especially if occupational asthma has developed.
    6.7.2) TREATMENT
    A) BRONCHOSPASM
    1) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) Irrigate the eyes for at least 15 minutes using only low pressure normal saline, with at least 1 liter per exposed eye. If normal saline is not available, immediately irrigate with similar quantities of tepid tap water.
    1) If symptoms persist, the patient should be referred to a health care facility for ophthalmological evaluation and management.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) Vigorous washing with soap and water is necessary, because hexachlorophene is well absorbed following dermal exposure and may remain on the skin following simple rinsing due to its poor water solubility (Shemano & Nickerson, 1954).

Enhanced Elimination

    A) URINARY ALKALINIZATION
    1) Urinary alkalinization may favorably alter tissue distribution of hexachlorophene and enhance its renal excretion (based only on one rat study; there are no human efficacy data) (Flanagan et al, 1995).
    B) HEMODIALYSIS
    1) Hemodialysis is probably not effective due to rapid redistribution of hexachlorophene into body lipid stores.
    C) PERITONEAL DIALYSIS
    1) Hexachlorophene is not significantly cleared by peritoneal dialysis (Boehm & Czajka, 1979).

Abstracts

Case Reports

    A) ROUTE OF EXPOSURE
    1) ORAL
    a) Following ingestion of 4 to 5 oz of a 3% hexachlorophene solution, a 6-year-old child became obtunded. Hypotension and seizures ensued, and death occurred within an hour of ingestion (Lustig, 1963).
    b) A woman accidentally ingested 200 mL of a detergent emulsion containing 3% hexachlorophene prior to abdominal hysterectomy. The patient vomited once during the operation and once afterwards. She became febrile, lethargic, confused, and died. Blood hexachlorophene level was 35 mcg/mL (Henry & DiMaio, 1974).
    c) Herskowitz and Rosman (1979) reported an 8-day-old infant who ingested 10 to 15 mL of a 3% solution (approximately 100 mg/kg) as a single dose. The child vomited a milky fluid and had watery diarrhea. Gastric lavage with isotonic saline was performed within 1 hour of ingestion. At 6 hours the child was lethargic with decreased response to pain. At 8 hours she continued vomiting and had diarrhea, and dehydration, as well as increased jitteriness and excitability. Plasma levels of 88 and 50 mcg/mL were measured at 24 and 48 hours, respectively. On the 6th day, symptoms resolved and the neurologic exam appeared normal. At a 2-1/2 year follow-up, no residual effects were seen (Herskowitz & Rosman, 1979).
    2) INHALATION
    a) Following frequent inhalation of hexachlorophene-containing powder for 15 years, a 43-year-old pediatric nurse developed occupational asthma triggered by hexachlorophene (Nagy & Orosz, 1984).
    3) DERMAL
    a) Marquardt (1986) reported a 6-year-old, 20 kg girl with 55% total body area second and third degree burns treated for one day with hexachlorophene 3% solution. The patient developed focal and generalized major motor seizures, and had continued aggressive behavior with diminished responsiveness to the environment. Blood hexachlorophene level one day following clinical deterioration was 2.98 mcg/mL (Marquardt, 1986).
    b) Chilcote et al (1977) reported death of a 10-year-old boy from hexachlorophene toxicity following topical treatment for 13 days for skin burns. Symptoms began on the 9th day of therapy. Temperature increased to 38.9 degrees centigrade. Lower extremity weakness developed and the patient became confused. Apnea developed on the 13th postburn day. Resuscitation was attempted, but the patient died 36 hours after the last hexachlorophene treatment. Aspiration pneumonia and nonspecific cerebral edema were noted at autopsy (Chilcote et al, 1977).

Range Of Toxicity

Summary

    A) TOXICITY: The minimal toxic or lethal dose following acute ingestion or repeated skin application is not well defined. Acute ingestion of large amounts (greater than 30 mL by adults) or repeated ingestion of small amounts may cause significant toxicity or death. Anorexia, vomiting, abdominal pain, diarrhea, dehydration, seizures, hypotension, shock, and death have been reported following inadvertent ingestion of 1 to 4 oz (30 to 120 mL) of 3% hexachlorophene. Following ingestion of 4 to 5 oz (120 to 150 mL) of a 3% hexachlorophene solution, a 6-year-old child became obtunded. Hypotension and seizures ensued, and death occurred within an hour of ingestion.
    B) THERAPEUTIC DOSES: 5 mL emulsion used topically for 3 minutes.

Therapeutic Dose

    7.2.1) ADULT
    A) TOPICAL
    1) 5 mL emulsion used topically for 3 minutes (Prod Info pHisoHex(R) topical detergent cleanser, 2011).
    7.2.2) PEDIATRIC
    A) Hexachlorophene should not be used for bathing infants. Infants, especially premature infants and those with dermatoses, are particularly susceptible to hexachlorophene absorption (Prod Info pHisoHex(R) topical detergent cleanser, 2011).

Minimum Lethal Exposure

    A) Acute ingestion of large amounts (greater than 30 mL by adults) or repeated ingestion of small amounts may also cause significant toxicity or death.
    B) Anorexia, vomiting, abdominal pain, diarrhea, dehydration, seizures, hypotension, shock, and death have been reported following accidental ingestion of 1 to 4 oz (30 to 120 mL) of hexachlorophene (Prod Info pHisoHex(R) topical detergent cleanser, 2011).
    C) CASE REPORTS
    1) Death occurred following ingestion of 1 gram (43 mg/kg) of hexachlorophene by a 7-year-old child (Boehm & Czajka, 1979).
    2) Following ingestion of 4 to 5 oz of a 3% hexachlorophene solution, a 6-year-old child became obtunded. Hypotension and seizures ensued, and death occurred within an hour of ingestion (Lustig, 1963).
    3) POTENTIAL TOXIC DOSES
     REFPT AGEPT WT (KG)DOSE (TOTAL)OUTCOME
    ORAL EXPOSURE17 yr231 g over 52 hr = 43 mg/kgblindness, bradycardia, respiratory failure, death
    28 days2.810-15 mg of 3% HCP (approx 100 mg/kg)recovered
    3adult---20 mg/kg/day x 3 days1 of 8 patients became comatose but recovered
    46 yrs16.4250 mg/kg - 4 to 5 oz of a 3% solutionhypotension, seizures, death
    517 days3.5250 mg/kg over 7 daysrecovered
    DERMAL EXPOSURE 6infants 3 mo to 3 yr Unknown portion of 200 g containers of powder each with 6.3% HCPfatal in 36/204
    76 yrs20Topical 3% HCP applied to areas of healing second and third degree burnsAcute onset of seizures with persisting agitation and neurobehavioral abnormalities
    REFERENCES -
    1 - Boehm & Czajka, 1979
    2 - Herskowitz & Rosman, 1979
    3 - Liu cited by Kimbrough, 1971
    4 - Lustig, 1963
    5 - Pilapil, 1966
    6 - Martin-Bouyer et al, 1982
    7 - Marquardt, 1986

    a) REFERENCES: (Marquardt, 1986; Martin-Bouyer, 1982; Boehm & Czajka, 1979; Herskowitz & Rosman, 1979; Kimbrough & Gaines, 1971; Pilapil, 1966; Lustig, 1963)
    D) ANIMAL DATA
    1) MICE: Given a dose of 60 milligrams/kilogram/day developed hepatic failure. Within 3 to 5 days, hind limb weakness proceeded to paralysis. By 6 to 7 days, drowsiness, listlessness, and weight loss became apparent (Prasad et al, 1987c).

Maximum Tolerated Exposure

    A) Anorexia, vomiting, abdominal pain, diarrhea, dehydration, seizures, hypotension, shock, and death have been reported following accidental ingestion of 1 to 4 oz (30 to 120 mL) of hexachlorophene (Prod Info pHisoHex(R) topical detergent cleanser, 2011).
    B) CASE REPORTS
    1) Herskowitz and Rosman (1979) reported an 8-day-old infant who received 10 to 15 mg of a 3% solution (approximately 100 mg/kg) as a single dose. At a follow-up examination after 2-1/2 years, no residual effects were seen (Herskowitz & Rosman, 1979).
    C) ANIMAL DATA
    1) Rats fed 500 ppm (25 mg/kg/day) of hexachlorophene in the diet had weakness in the hindquarters which progressed to paralysis. When the poisoned diet was discontinued, the animals gradually recovered over a period of weeks (Lewis, 2000).

Workplace Standards

    A) ACGIH TLV Values for CAS70-30-4 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS70-30-4 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS70-30-4 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Hexachlorophene
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 3 ; Listed as: Hexachlorophene
    a) 3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS70-30-4 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (INTRAPERITONEAL)MOUSE:
    1) 20 mg/kg
    B) LD50- (ORAL)MOUSE:
    1) 67 mg/kg
    C) LD50- (SKIN)MOUSE:
    1) 270 mg/kg
    D) LD50- (INTRAPERITONEAL)RAT:
    1) 22 mg/kg
    E) LD50- (ORAL)RAT:
    1) 56 mg/kg
    F) LD50- (SKIN)RAT:
    1) 1840 mg/kg
    G) LD50- (SUBCUTANEOUS)RAT:
    1) 7650 mcg/kg
    H) HUMAN DATA

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Hexachlorophene is a chlorinated bisphenol compound which has been widely used as a topical antiseptic and preoperative surgical scrub, although its use has been curtailed since the 1970's.
    B) With topical application, hexachlorophene accumulates on the skin leaving a residue which makes it an effective agent against colonization with gram-positive organisms (Kopelman, 1973). It is well absorbed both orally and percutaneously, and is highly lipophilic.

Toxicologic Mechanism

    A) Hexachlorophene toxicity is more common following ingestion, although it may occur following topical use. Toxicity most commonly affects the skin, the GI tract, and the nervous system.
    B) Acetylcholinesterase inhibition in vitro has been described in sheep brain tissue (Prasad et al, 1987a). Increased cerebral gamma-amino butyric acid (GABA) levels have been reported in mice (Prasad et al, 1987b).
    C) Hexachlorophene is neurotoxic, causing paralysis associated with edema and spongiform degeneration of cerebral white matter (spongiform encephalopathy) (Lockhart, 1972; Shuman et al, 1973).

Physicochemical

Physical Characteristics

    A) Hexachlorophene is a crystalline solid (from benzene) or a white to light tan powder (Budavari, 1996; Lewis, 1997; HSDB , 2002).
    B) It is white to light tan in color (HSDB , 2002).
    C) It is odorless or has a slight phenolic odor (CHRIS , 1997; HSDB , 2002).
    D) Hexachlorophene is tasteless (HSDB , 2002).

Ph

    1) No information found at the time of this review.

Molecular Weight

    A) 406.92 (Budavari, 1996)

References

General Bibliography

    1) 40 CFR 372.28: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Lower thresholds for chemicals of special concern. National Archives and Records Administration (NARA) and the Government Printing Office (GPO). Washington, DC. Final rules current as of Apr 3, 2006.
    2) 40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.
    3) 49 CFR 172.101 - App. B: Department of Transportation - Table of Hazardous Materials, Appendix B: List of Marine Pollutants. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 29, 2005.
    4) 49 CFR 172.101: Department of Transportation - Table of Hazardous Materials. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 11, 2005.
    5) 62 FR 58840: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 1997.
    6) 65 FR 14186: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    7) 65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    8) 65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    9) 66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.
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